Adherence, carbohydrate polymer production, acidogenesis, and acidurance are virulence properties associated with the cariogenic bacterium Streptococcus mutans. Each of these properties contributes to some degree to the virulence of this organism. Little if anything is known about how this organism regulates the transcription and translation of its genes or what molecular mechanisms are utilized by this pathogen to adapt to different environmental stimuli. This proposal seeks to develop an efficient and effective system for the identification and isolation of the operators that comprise selected global regulons of S. mutans. Once developed, this system will be utilized for the dissection of global regulatory networks, with specific emphasis on those characteristics of S. mutans that are essential for the disease process. The techniques to be used involve genetic engineering, transposon mutagenesis, gene fusions, and reporter gene technology.